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CASE REPORT

From the Department of Pediatrics* & Medicine** , Acharya Shri Chander College of Medical Sciences, Sidhra, JammuCorrespondence to : Dr Ravinder K Gupta , Professor, Deptt. of Pediatrics, ASCOMS , Sidhra, Jammu, J & K - 180017

Neurotuberculosis as a Cause of ObesityRavinder K Gupta *, Sanjay Bhat**, Asma Saheen *

Hypothalamus, the most evolutionary conservedregions of mammalian brain involved in maintaininghomeostasis of life, integrates sensory and hormonal inputsand provides coordinated responses through motor outputsto key regulatory sites. The patterned outputs to variouseffector sites result in coordinated endocrine ,behavioral,and autonomic responses to maintain the homeostasis.(1,2) Leptin , an established mediator of body weightand other neuroendocrine functions, is secreted by adiposecells. Its high levels decrease food intake and increaseenergy expenditure. The childhood obesity which is takingthe form of pandemic is multifactorial,i;e various genetic,anatomic, environmental factors are implicated to thisdisease (1-4). While evaluating the cause of obesity in achild, in addition to the common causes, diseases involvinghypothalamus should not be overlooked . We arediscussing here 9 year male child who reported to us forobesity and neurotuberculosis as the etiology wasestablished.Case Report

A 9 year male child , 2nd in birth order, born to aconsanguineous marriage, presented with history ofsignificant weight gain, lethargy, vague pain in both lowerlimbs and loss of interest in the surroundings for last 6months. There was history of hyperphagia along withphysical inactivity. There was no history of fever, rash,swelling in any joint. History of contact with patient ofpulmonary Koch's was present .There was no history of

AbstractChildhood obesity, taking the form of pandemic in the present era owing to the food habits, lifestyle etc, isthe main cause of adult onset diseases. Obesity is the major risk factor for insulin resistance and diabetes,hypertension, cancer, gall bladder disease, and atherosclerosis in adulthood. Obesity being multi-factorialvarious genetic, anatomic, environmental factors are implicated to its etiognesis. While evaluating thecauses of obesity in a child, in addition to the common causes, diseases involving hypothalamus should notbe overlooked. We are discussing here a 9 year male child who reported to us for obesity andneurotuberculosis as the etiology was established.

Key WordsObesity, Neurotuberculosis, Hypothalamus

Introductionabnormal weight gain in the family. Antenatal and perinatalhistory was normal. Milestones were consistent with ageprior to illness. On examination the child was conscious,cooperative and well oriented. Vitals were normal.General physical examination was normal, no peculiarfacies was noted. BCG scar was absent. Systemicexamination did not reveal anything abnormal clinically.Tanner stage was, Pubertal 1, Gonadal 1 and Testicularvolume-4-6ml.Eye examination including fundus and ENTexamination were normal. Anthropometry: Weight 40 kg(as expected 25-27 kg), Height 125cm , Upper Segment:Lower Segment ratio 1:1, Head circumference 53cm,Chest circumference 77cm, Mid arm circumference20cm, Body Mass Index(BMI) 25.64 Kg/Sq.m(greaterthan 95th percentile for the age)

Investigations revealed Hb 10gm%, Total LeucocyteCount- 9000/cu.mm, Differential Leucocyte Count - P68L-30 E2, PBF- Normocytic normochromic, ESR 32 mm1st hr. Urine /Stool Routine examination- normal, Urinaryspecific gravity of 1020 and 24hr urine volume was1100ml(< 30ml/kg ).24 urinary cortisol( 50µg/24hrs ). 8a.m cortisol was 18microgms/dl. Renal and Liver FuntionTests, Lipid profile, Thyroid profile were within normalrange. FSH (10.2mIU/ml), LH(11.3mIU/ml) werenormal. X-ray chest- prominent hilar shadows withparenchymal lesion on right middle and lower lobessuggestive of consolidation. Mantoux reading 22 mm after72 hours. Ultrasound abdomen revealed no abnormality.

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CSF exam: proteins-64mg%, glucose -56 mg%(Bloodglucose-85mg%), 5 cells/hpf (lymphocytes), no AFBseen. Contrast enhanced MRI study revealed thepresence of multiple thick walled ring enhancing lesionsin the brain surrounded by edema and presence of arounded non -enhancing cystic lesion in the suprasellarregion. (Fig-2&3) The findings were highly suggestiveof multiple granulomatous lesions (tuberculomas). In viewof history and examination, investigations and radiologicalprofile, a diagnosis of neurotuberculosis with obesitywas made. The child was put on Anti tubercular Therapy(ATT) with steroids and supportive therapy. During thecourse of stay in hospital child's general activity improved,generalized body aches and lethargy decreased andappetite became normal.

cause dysregulation of the Leptin pathway andconsequently food seeking behavior like hyperphagia aswas seen in this particular child.

Tuberculosis, a major global public health issue owingto its resurgence due to HIV pandemic in both developingand developed countries, has been estimatedapproximately 10% for CNS involvement. In developingcountries CNS tuberculosis is a disease of younger agegroup, usually childhood (5).Most tuberculous infectionsof the CNS are caused by Mycobacterium tuberculosis.Less frequently, other mycobacteria may be involved. Itis believed that the bacilli reach the CNS by thehaematogenous route secondary to disease elsewhere inthe body. Initially small tuberculous lesions (Rich's foci)develop in the CNS, either during the stage of bacteraemiaof the primary tuberculous infection or shortly afterwards(6). These initial tuberculous lesions may be in themeninges, the subpial or subependymal surface of thebrain or the spinal cord, and may remain dormant foryears after initial infection. Later, rupture or growth ofone or more of these small tuberculous lesions producesdevelopment of various types of CNS tuberculosis.Rupture into the subarachnoid space or into the ventricularsystem results in meningitis. The type and extent of lesionsthat result from the discharge of tuberculous bacilli intothe cerebrospinal fluid (CSF), depend upon the numberand virulence of the bacilli, and the immune response ofthe host.

It has been suggested that with a sizeable inoculationor in the absence of an adequate cell-mediated immunity,the parenchymal cerebral tuberculous foci may develop

Fig. 2 & 3 Contrast Enhanced MRI Study Showing Pres-ence of Multiple Thick Walled ring Enhancing lesions in theBrain Surrounded by Edema and Presence of a RoundedNon –Enhancing Cystic Lesion in the Suprasellar Region

DiscussionObesity as defined by BMI exceeding 95th Percentile,

age gender specific , represents a heterogeneous groupof conditions with multiple causes (1-4). Body weight isdetermined by complex interaction between genetic,environmental, and anatomic factors.

Aetiology of obesity may be attenuated or exacerbatedby non-genetic factors which may include both infectiveand non-infective causes.

Leptin which is produced by adipose tissue plays acentral role in the long-term maintenance of weighthomeostasis by acting on the hypothalamus by decreasingfood intake and increasing energy expenditure. Leptinsuppresses expression of hypothalamic neuropeptide Y,a potent appetite stimulatory peptide, and it also increasesthe expression of MSH, which acts through the MC4Rmelano-cortin receptor to decrease appetite. Thus, leptinactivates a series of downstream neural pathways thatalter food-seeking behavior and metabolism (1-4).Diseases infective/non infective involving hypothalamus

Fig.1 A 9 Year male Obese Child with Neurotuberculosis as the Etiology

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1 Sheila Gahagan: Overweight and Obesity. In.Robert M.Kliegman, Richard E., Behrman, Nina F. Schor and BonitaF.Stanton (eds): Nelson Textbook of Pediatrics.19th ed.WB Saunders .Philadelphia; 2011.pp. 179-88.

2. Tank S,Chauhan P H. Obesity. In : Gupte S (ed) RecentAdvances of Pediatrics ,Special Vol 13 PediatricEndocrinology. Jaypee Brothers. New Delhi. 2004.pp.108-125

3. Bessesen DH. Update on Obesity. J Clin Endocrinol Metab2008; 93 (6): 2027-34

4. Speiser PW, Rudolf MC, Anhalt H, et al. ChildhoodObesity. J Clin Endocrinol Metab 2005;90 (3): 1871-87

5. Dastur DK, Manghani DK, Udani PM. Pathology andpathogenetic mechanisms in neuro-tuberculosis. Radiol ClinNorth Am 1995; 33:733-52.

6. Udani PM Neurotuberculosis : Pathology and Pathogenesis.In Essential of Tuberculosis in children. Vilesh seth , SKKabra (eds) 3rd edn Jaypee Brothers . New Delhi .2006.pp.221-222

7. Ahuja GK, Mohan K K, Prasad K, Behari M. Diagnosticcriteria for tuberculous meningitis and their validation.Tubercle Lung Dis 1994; 75:149-52.

8. Snider DE, Rieder HL, Combs D, Bloch AD,Hayden CH.Tuberculosis in children. Pediatr Infect Dis J 1988; 7:271-8.

9. Garg RK . Tuberculosis of the central nervous system.Postgrad Med J 1999; 75:133-140

10. Rajshekhar V, Chandy MJ. Tuberculomas presenting asisolated intrinsic brain stem masses. Br J Neurosurg 1997;11:127-33.

11. Gupta RK Gupta R. Neurotuberculosis .In: Gupte S(ed).Recent Advances in Pediatrics .Special vol.18 PediatricNeurology. Jaypee Brothers. New Delhi 2008.pp.151- 171

into tuberculomas.(5-8) Tuberculomas are firm, avascular,spherical granulomatous masses, measuring about 2-8cm in diameter. They are well limited by surrounding braintissue which is compressed around the lesion and showoedema and gliosis. The inside of these masses maycontain necrotic areas composed of caseous material,occasionally thick and purulent, in which tubercle bacillican be demonstrated.

Intracranial tuberculomas can occur at any age. Indeveloping countries young adults and children arepredominantly affected while in developed countries theyare more common in older patients. The symptomsproduced by tuberculoma are related to their location.Low-grade fever, headache vomiting, seizures, focalneurological deficit, and papilledema are characteristicclinical features. Hypothalamic-pituitary dysfunctiondevelops in a single/multiple supratentorial tuberculomas.Infra-tentorial tuberculomas are more common in childrenand may present with brainstem syndromes, cerebellarmanifestations,and multiple cranial nerve palsies.(5)

On CT scan, tuberculomas are characterised as lowor high-density lesions, rounded or lobulated masses andshow intense homogenous or ring enhancement aftercontrast administration. They have an irregular wall ofvarying thickness .Moderate to marked peri-lesionaloedema is frequently present. Tuberculomas may besingle or multiple and are more common in frontal andparietal lobes, usually in parasagittal areas. On CT scan,the 'target sign', a central calcification or nidus surroundedby a ring that enhances after contrast administration,isconsidered pathognomonic of tuberculomas(6-9). Indeveloping countries like India, tuberculomas arefrequently confused with cysticercus granuloma.Stereotactic diagnostic biopsy can help in establishing anaccurate diagnosis in significant proportion of patientswho had tuberculomas in childhood. Because earlydiagnosis and appropriate replacement therapy can be ofgreat benefit to these patients, and prevent them fromdevelopment of hypopituitarism.(10)

Obesity, hypogonadism, Frolich syndrome, sexualprecoccity, diabetes inspidus, and growth retardation havebeen reported after tubercular meningitis. Hypothalamusalso controls the regulation of food intake. The lateralarea of tubercinerium acts as a center for hunger orappetite, while the ventromedial nucleus of the thalamusis considered with satiety. Damage to the latter affectssatiety with the result that the child develops voraciousappetite and obesity. This is seen long after steroid therapyis omitted in a child with TBM and may appear evenafter months.(6,9,11) This might be the possibility in our

case in development of obesity followingneurotuberculosis.Conclusion

Any child coming for evaluation of obesity,neurotuberculosis as the cause of obesity should be keptin mind and accordingly investigated . The variedmanifestations of CNS tuberculosis, a commonneurological disorder in developing countries, have nowbecome relevant in other parts of the world ,as the wholespectrum of these disorders is now being reportedworldwide. The increasing problem of drug resistancehas added a new challenge. The early recognition andtimely treatment of the disease is critical as theconsiderable mortality and morbidity associated with thecondition can be prevented.

References